Aspirin, paracetamol (acetaminophen) and caffeine for the treatment of acute migraine attacks: A systemic review and meta‐analysis of randomized placebo‐controlled trials

BACKGROUND AND PURPOSE: Many migraine patients rely on over-the-counter analgesics for the treatment of migraine attacks. Fixed-dose combinations of aspirin, paracetamol and caffeine (APC) have been used for treating migraine in many countries for a long time. We performed a meta-analysis for the comparison of APC versus placebo, which has not been done to date. METHODS: Randomized, blinded, placebo-controlled, parallel-group studies using APC to treat a migraine attack were included in a meta-analysis. We calculated the rate ratio (RRs) associated with APC versus placebo. RESULTS: Seven studies were included, with 3306 participants (2147 treated with APC and 1159 treated with placebo). For the primary efficacy outcome, being pain-free at 2 h, APC was superior to placebo (19.6% vs. 9.0%, RR 2.2, 95% confidence interval [CI] 1.4-3.3). For the co-primary efficacy outcome, pain relief at 2 h, APC was superior to placebo (54.3% vs. 31.2%, RR 1.7, 95% CI 1.6-1.9). Adverse events were more frequent in the APC than the placebo groups (10.9% vs. 7.8%, RR 1.7, 95% CI 1.3-2.2). CONCLUSIONS: Results showed that APC is superior to placebo in the treatment of acute migraine attacks. Efficacy, measured by pain-free response and pain relief at 2 h, was clinically relevant.